The SH2 (Src Homology 2) domain is a
structurally conserved protein interaction domain contained within 110 human and mouse proteins. Proteins containing SH2 domains are found in many intracellular signaling proteins. SH2 domains typically bind a phosphorylated tyrosine
residue in the context of a longer peptide motif within a target
protein, and SH2 domains represent the largest class of known
pTyr-recognition domains. The function of SH2 domains is to specifically recognize the
phosphorylated state of tyrosine residues, thereby allowing SH2
domain-containing proteins to localize to tyrosine-phosphorylated sites.
This process constitutes the fundamental event of signal transduction
through a membrane, in which a signal in the extracellular compartment
is "sensed" by a receptor and is converted in the intracellular
compartment to a different chemical form, i.e. that of a phosphorylated
tyrosine. Tyrosine phosphorylation leads to activation of a cascade of
protein-protein interactions whereby SH2 domain-containing proteins are
recruited to tyrosine-phosphorylated sites. This process initiates a
series of events which eventually result in altered patterns of gene
expression or other cellular responses. The SH2 domain, which was first
identified in the oncoproteins Src and Fps, is about 100 amino-acid
residues long. It functions as a regulatory module of intracellular
signaling cascades by interacting with high affinity to
phosphotyrosine-containing target peptides in a sequence-specific and
strictly phosphorylation-dependent manner |